JP6781358B1 - Foamable topical composition - Google Patents

Abstract

Provided is an external composition containing a polymer surfactant as a foaming component to form a foam during use. The external composition of the present application is provided by filling, for example, a pump former container or a squeeze former container.

Description

The present invention relates to an external composition that forms bubbles during use.

Conventionally, ointments, creams, lotions, etc. have been used as external medicines to be used on the skin (including the scalp), but in recent years, they can be easily applied without dripping and spread smoothly. Aerosol-type preparations that eject in the form of foam using a foaming liquid and a propellant have been developed because of their excellent usability. However, since this aerosol-type preparation uses liquefied gas such as liquefied propane as a propellant, it is subject to restrictions on volatile organic compounds, and used cans cannot be used repeatedly in terms of the environment. There is a problem, and recently, a non-gas type formulation that exhibits a foamy shape at the time of discharge has been developed using a pump former container or a squeeze former container.

Generally, a surfactant is known as a component that forms bubbles. Anionic surfactants are said to have high foaming power but are irritating, and nonionic surfactants are said to be low irritating but low foaming power, and are a kind of surfactant. No one has been obtained that satisfies both foaming power and safety. Combining polyoxyethylene alkyl ether and / or polyoxyethylene alkenyl ether with polyoxyethylene fatty acid ester and / or polyoxyethylene cured castor oil as a nonionic surfactant to form a safe and good foam. (Patent Document 1).

JP-A-2017-214407

However, in order to reduce the burden on the skin, it is preferable that the amount of additives is small, and with less additives, it is possible to produce better foam quality, moderate foam retention without dripping, and comfortable foam. The development of a new foaming external composition is strongly desired.

An object of the present invention is to provide a foamable external composition capable of producing a foam having better foam quality, an appropriate foam holding feeling without dripping, and a comfortable feeling in use.

The present inventors have conducted intensive research in view of such a situation, and have found that the desired purpose can be achieved by using a polymer surfactant as a foaming agent. That is, the present invention relates to an external composition containing a polymer surfactant as a foaming component and forming bubbles during use.

As is clear from the results of the examples described later, the formulation of the present invention can obtain a new external composition having better foam quality, moderate foam retention without dripping, and good usability, especially gas. It can be used as a non-gas type preparation that foams when discharged by using a pump former container or squeeze former container that does not require it, and a composition suitable for the treatment of skin diseases such as atopic dermatitis can be obtained. It was.

It is a photograph which shows the result (foam formation) of Example 1. It is a photograph which shows the result of Example 2 (foam persistence (evaluated by polyurethane)). It is a photograph which shows the result of Example 2 (sustainability of foam (evaluation by Kim towel)). It is a photograph which shows the result (dripping of foam) of Example 2.

The external composition of the present invention can be used as a spray agent for foaming the undiluted solution at the time of use and spraying it on the skin, or as a base thereof. The undiluted solution means a liquid composition capable of foaming. The external composition of the present invention can be used by using a foam discharge container that sprays the stock solution in the container with a pump without using a propellant. The foam discharge container is not particularly limited as long as the composition of the present invention can be mixed with air and discharged in a foamed state. For example, a pump spray (pump former) container or a soft container that discharges from a pressing pump. A squeeze former container or the like that presses and discharges the body portion is preferably used.

The polymer surfactant of the present invention includes cellulose derivatives such as ethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose (hypromellose), carboxymethyl cellulose, sodium carboxymethyl cellulose, and carboxymethyl ethyl cellulose, polyvinyl alcohol, polyvinylpyrrolidone, and polyethylene. It is at least one selected from glycol and polyacrylic acid. Preferably, at least one selected from cellulose derivatives, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol and polyacrylic acid, more preferably from hydroxypropylmethylcellulose, hydroxyethylcellulose, methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol and polyacrylic acid. At least one selected, especially hydroxypropyl methylcellulose (hypromellose), is preferred. As the hypromellose, those having a substitution degree type of 2906 or 2910 specified in the Japanese Pharmacopoeia are preferably used. The polymer surfactant is 0.01 to 10% by weight, preferably 0.1 to 5% by weight, more preferably 0.2 to 3% by weight, particularly about 0.5% by weight, based on the total amount of the composition. , About 0.75% by weight and about 1% by weight are exemplified. In addition, in the present specification and claims, when the numerical value is referred to as "about", it shall include up to ± 20%, ± 10% or ± 5% of the indicated numerical value. According to the present invention, a desired effect can be achieved with only one type of polymer surfactant.

In addition to the above-mentioned polymer surfactants, the compositions of the present invention include other surfactants that can be used in the pharmaceutical and cosmetic fields, for example, anionic surfactants, cationic surfactants, and amphoteric surfactants, if desired. Agents and nonionic surfactants may be added. Anionic surfactants include, for example, N-acyl-N-methylglycine salt, sodium alkylsulfonate, sodium alkylsulfate, polyoxyethylene alkyl ether carboxylate, sodium lauryl sulfate, and the like as cationic surfactants. Examples of amphoteric surfactants such as benzalkonium chloride, benzethonium chloride, aliphatic amine salts, and aliphatic quaternary ammonium salts include lauryldimethylaminoacetate betaine, stearyldimethylaminoacetate betaine, and 2-alkyl-N. Nonionic surfactants such as -carboxymethyl-N-hydroxyethyl imidazolinium betaine, lauryl dimethylamine oxide, lauric acid amidopropyl betaine, cocamidopropyl betaine, and lauryl hydroxysulfobetaine include, for example, polyoxyethylene alkyl. Ether, polyoxyethylene alkenyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene fatty acid glyceryl, polyoxypropylene polyoxyethylene alkyl ether and polyoxypropylene polyoxyethylene alkenyl Examples include ether.

The composition of the present invention may contain alcohol. Alcohols include monohydric alcohols such as ethanol and isopropyl alcohol, polyethylene glycol, glycerin, 1,3-butylene glycol, erythritol, sorbitol, xylitol, martitol, propylene glycol, dipropylene glycol, diglycerin, isoprene glycol, 1, Polyhydric alcohols such as 2-pentanediol, 2,4-hexanediol, 1,2-hexanediol, and 1,2-octanediol are exemplified and may contain one or more. In particular, glycerin, propylene glycol, polyethylene glycol, and 1,3-butylene glycol are preferably exemplified. The total content of the alcohol is 5-60% by weight, preferably 10-50% by weight, more preferably 15-40% by weight.

The composition of the present invention preferably has a pH value in the range of 3-12. A more preferable pH value is 4 to 10. Examples of the pH adjusting agent for adjusting the pH value of the composition to the above range include potassium dihydrogen phosphate, citric acid and the like, which are used for adjusting to the low pH range, and are used in the high pH range. Those used for regulation include sodium hydroxide, potassium hydroxide, sodium lactate, sodium citrate, L-arginine, diisopropanolamine and the like. Particularly preferable pH adjusters include potassium dihydrogen phosphate, potassium hydroxide, sodium citrate, citric acid, diisopropanolamine, sodium edetate and the like.

In addition to the above components, the liquid composition according to the present invention includes additives generally used for external preparations for skin such as preservatives (preservatives), antioxidants, wetting agents, stabilizers, and ultraviolet absorbers. Can include agents.

Examples of the above-mentioned preservatives include paraoxybenzoic acid esters (parabens) such as methyl paraoxybenzoate, ethyl paraoxybenzoate, and propyl paraoxybenzoate, sodium benzoate, phenoxyethanol and the like. The above preservative may be used alone or in combination of two or more. The content of the preservative in the composition is preferably in the range of 0.01 to 1% by weight, more preferably in the range of 0.1 to 0.5% by weight.

The composition of the present invention may be provided as a base for producing a pharmaceutical product or cosmetic by blending a pharmaceutical active ingredient or an ingredient effective as a cosmetic, and the composition of the present invention contains a pharmaceutical active ingredient. You may be. A composition containing a pharmaceutical active ingredient is also one of the aspects of the present invention.

The composition of the present invention is used as an external preparation applied to the skin for treating skin inflammation, eczema, atopic dermatitis, psoriasis, acne, scars, decubitus, acne, etc. (healing, improving symptoms, etc.) It is suitably applied to skin diseases such as prevention of deterioration and prevention of onset), and is also suitable for application not only to the skin but also to hairy parts such as the scalp.

The active ingredient to be blended in the composition of the present invention is not particularly limited as long as it is applied to the skin, but steroids, non-steroidal anti-inflammatory agents, bactericidal agents, antibacterial agents, and antifungal agents. Examples thereof include agents, vitamins, immunosuppressants, mucopolysaccharides, cAMP derivatives, fibroblast growth factors, naphthoic acid derivatives, benzoyl peroxide and the like. The steroids are not particularly limited as long as they have a steroid skeleton, but the non-steroid anti-inflammatory such as cortisone, hydrocortisone, fludrocortisone acetate, prednisolone, methylprednisolone, dexamethasone, betamethasone, clobetazol and derivatives thereof. Examples of the agent include indomethacin, sprofen, ketotiphen, allantin, dipotassium glycyrrhizinate, etc., the bactericidal agent includes chlorhexidine gluconate, benzalkonium chloride, etc., and the antibacterial agent includes tetracycline hydrochloride, chloramphenicol, sulfuric acid, etc. Fradiomycin, nadifloxacin, clindamycin phosphate, ozenoxacin, oxytetracycline hydrochloride, polymyxin B sulfate, etc., gentamycin sulfate, sodium fujicinate, etc. Examples of vitamins include vitamin A or a derivative thereof (for example, vitamin A oil), vitamin B or a derivative thereof (for example, pantenol), vitamin C or a derivative thereof, vitamin D or a derivative thereof (for example, active vitamin D3), and the like. Vitamin E or a derivative thereof (for example, tocopherol acetate, etc.), vitamin K or a derivative thereof, the immunosuppressant includes tachlorimus, cyclophosphamide, etc., and the mucopolysaccharide includes a heparin analog or hyaluronic acid. Examples of the salt and cAMP derivative include sodium bucladecine, the fibroblast growth factor includes trafermin, and the naphthoic acid derivative includes adaparene. These contents are 0.001 to 10% by weight, preferably 0.01 to 10% by weight, and more preferably 0.01 to 5% by weight. In particular, an external composition containing a heparin-like substance or a mucopolysaccharide such as hyaluronic acid and a salt thereof is preferably exemplified.

In particular, in the foaming composition containing a heparin-like substance, the heparin-like substance has a blood coagulation inhibitory effect, a blood flow increasing effect, a hematoma elimination promoting effect, a keratin water retention enhancing effect, and a fibroblast proliferation inhibitory effect. Dry skin disease, sebum deficiency, progressive finger palmar keratoderma, frost, hypertrophic scar / keloid, pain and inflammatory disease due to impaired circulation (coagulation and pain after injection), thrombotic venitis (including sprain) ), It is also suitable as a therapeutic composition for swelling, hematoma, tendon sheath inflammation, muscle pain, arthritis, muscular oblique neck, etc. after trauma (bruise, sprain, contusion).

The present application will be described in more detail below with experimental examples to clarify the effects of the present application, but these are merely examples, and the scope of the present application is not limited thereto.

Example 1
The prepared sample was filled in a pump former container according to the following formulation, and the presence or absence of foam formation during discharge from the container was evaluated (Table 1, FIG. 1).
Samples A to I and N are polymer surfactants.

The sources of each sample used in this example are shown below.

It was found that each of the polymer surfactants blended in the foaming external composition of the present invention is effective as a foaming agent alone.

Example 2
The prepared sample was filled in a pump former container according to the following formulation, and the presence / absence of foam formation, foam quality, foam retention time and presence / absence of dripping were measured (Tables 3 and 4). Under condition A, a polyurethane material mat was used as a material close to the skin of a healthy person, and under condition B, a Kim towel assuming relatively severe dry skin was used and discharged onto the mat (FIGS. 2 and 3). In addition, after discharging to a mat made of polyurethane material, it was tilted at about 45 ° C. and it was observed whether or not dripping occurred (FIG. 4).

Human profile Merosu is alone in forming a high-quality and stable foam, even after the 5 minute hold, even after 3 minutes was not dripping. This effect was further enhanced by the combination of polyhydric alcohols. On the other hand, the combination of polyoxyethylene cured castor oil 60 with polyoxyethylene cetyl ether or polyoxyethylene lauryl ether does not form bubbles or has low elasticity even if it is formed, has a short retention time, and drips. Even when combined with polyhydric alcohol, it was inferior in elasticity and retention time as compared with the preparation using hypromellose.

Example 3
The presence or absence of foam formation depending on the concentration was evaluated using hypromellose having different viscosities. The evaluation criteria for foam quality are the same as in Example 1.

Foam was formed at a concentration of 0.2% or more regardless of the viscosity of hypromellose.

Example 4
Two kinds of compositions containing a heparinoid at a concentration of 0.1 or 0.3% were prepared in the formulation shown in the raw material name 2 in Table 3 of Example 2, and filled in a pump former container to foam. The presence or absence of formation, the retention time of bubbles, and the presence or absence of dripping were measured ( Table 6 ).

As shown in Table 6 , using the composition of the present invention, a heparinoid-containing pharmaceutical composition having good foam quality in both texture and elasticity, and having moderate foam without dripping was obtained.

Claims (10)

A composition containing a polymer surfactant as a foaming component and 1,3-butylene glycol is filled in a pump former container or a squeeze former container, and a propellant is contained in the container. An external product that forms bubbles when used, which is characterized by the absence. The product according to claim 1, wherein the polymer surfactant is at least one selected from a cellulose derivative, polyvinyl alcohol, polyvinylpyrrolidone, polyethylene glycol, and polyacrylic acid. The product according to claim 2, wherein the cellulose derivative is at least one selected from hydroxypropylmethyl cellulose, hydroxyethyl cellulose, and methyl cellulose. The product according to claim 3, wherein the cellulose derivative is hydroxypropylmethyl cellulose. The product according to claim 4, which contains 0.2 to 3% by weight of hydroxypropylmethylcellulose and 15 to 40% by weight of 1,3-butylene glycol with respect to the total amount of the composition. The product according to any one of claims 1 to 5 , which contains at least one pharmaceutical active ingredient. The product according to claim 6 , wherein the pharmaceutically active ingredient is a mucopolysaccharide. The product according to claim 6 or 7 , wherein the content of the pharmaceutically active ingredient is 0.01 to 5% by weight based on the total amount of the composition. The product according to claim 8 , which contains a heparinoid and / or hyaluronic acid or a salt thereof as a pharmaceutically active ingredient. The product according to any one of claims 1 to 9 , for the treatment of skin diseases.

Images